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ID: ALA4342435

Journal: Bioorg Med Chem Lett

Title: Synthesis of novel 4-Boc-piperidone chalcones and evaluation of their cytotoxic activity against highly-metastatic cancer cells.

Authors: Ocasio-Malavé C, Donate MJ, Sánchez MM, Sosa-Rivera JM, Mooney JW, Pereles-De León TA, Carballeira NM, Zayas B, Vélez-Gerena CE, Martínez-Ferrer M, Sanabria-Ríos DJ.

Abstract: In this study, six curcuminoids containing a tert-butoxycarbonyl (Boc) piperidone core were successfully synthesized, five of them are novel compounds reported here for the first time. These compounds were prepared through an aldolic condensation by adding tetrahydropyranyl-protected benzaldehydes or substituted benzaldehyde to a reaction mixture containing 4-Boc-piperidone and lithium hydroxide in an alcoholic solvent. A 44-94% yield was obtained supporting the developed methodology as a good strategy for the synthesis of 4-Boc-piperidone chalcones. Cytotoxic activity against LoVo and COLO 205 human colorectal cell lines was observed at GI50 values that range from 0.84 to 34.7 μg/mL, while in PC3 and 22RV1 human prostate cancer cell lines, GI50 values ranging from 17.1 to 22.9 μg/mL were obtained. Results from biochemical assays suggest that the cytotoxicity of the 4-Boc-piperidone chalcones can be linked to their ability to induce apoptosis, decrease the activity of NFκB and cellular proliferation. Our findings strongly support the potential of Boc-piperidone chalcones as novel cytotoxic agents against highly-metastatic cancer cells.

CiteXplore: 31767266

DOI: 10.1016/j.bmcl.2019.126760